Among various known dosage forms such as tablets and capsules, granular preparations such as granules and powders have a great role to play. That is, a granular preparation is of great advantage in that a dose can be varied freely, it is easy to take for children and the aged, and compliance can be improved. In view of the fast expanding number of the aged patients in recent years, the demand for granular preparations has been increasing.
On the other hand, even granular preparation is not always easy to take when they contain a medicine having an unpleasant taste. Various pharmaceutical techniques have been proposed to solve this problem. The most frequently used technique is to coat the surface of particles with a coating agent which does not dissolve in the mouth, such as wax or water-insoluble polymers. The coating agent of this type has been applied by spray coating in the form of a solution in an organic solvent. However, use of an organic solvent involves many problems, such as adverse influence on workers' health, environmental pollution, and remaining solvent in the preparation. Hence, a method of using an aqueous coating composition prepared by dispersing a coating agent in water together with a plasticizer has been developed and used extensively. However, this method is still unsuitable for those substances which are unstable against water. Besides, where the method is applied to a medicine easily soluble in water, the medicine is easily dissolved in the coating composition. As a result, the particles tend to adhere to each other during coating to form agglomerates, or a coating layer cannot be formed sufficiently. Further, where the coating composition is applied by spray coating, there are so many variable manufacturing conditions, such as coating speed, temperature, and the like. Therefore, highly precise process control is required in order to obtain preparation with a constant quality.
Apart from the above-mentioned coating technique, a melt coating method has been proposed for the purpose of masking bitterness, in which a finely powdered medicine is melt-granulated together with glycerol monostearate, which is an oily substance, with or without a finely powdered diluent, and the resulting particles are prepared by melt coating with a coating agent consisting solely of talc. It has turned out, however, that the particles prepared by this method tend to cake with time when exposed to heat and humid conditions.
It is known that, in general, particles containing an oily substance cake when storaged at or below the melting point of the oily substance (see Wakiyama Naoki, Pharm. Tech. Japan, Vol. 10, p. 819 (1994)). It is reported said that such factors as the particle size and the oily substance content have influences on caking of the particles. As an approach to preventing granular preparations from agglomeration and caking, addition of a small amount of a finely powdered additive was proposed (see P. York, J. Pharm. Sci., Vol. 64, pp. 1216-1221 (1975)), S. Dawoodbhai and C. T. Rhodes, Drug Dev. Ind. Pharm., Vol. 16, pp. 2409-2429 (1990), and G. Gold, et al., J. Pharm. Sci., Vol. 57, pp. 667-671 (1968)). It has been reported, however, that the addition of a small amount of a finely powdered additive to an oily substance-containing particle system induces a peculiar phenomenon that fluidity of the particles decreased, and further their caking increased (Wakiyama Naoki, ibid).
An object of the invention is to provide a granular preparations which does not cake even under heat and humid conditions and in which an unpleasant taste of a medicine can be masked.